Monkey See, Monkey Juice

Week in Review / by Evan Lerner /

An elegant gene therapy trial “cures” colorblindness in monkeys and new film about Darwin attempts to drum up some controversy.

Illustration: Mike Pick

A paper published in the most recent Nature revealed this week’s big scientific finding: Gene therapy can cure colorblindness in male squirrel monkeys.

The cones that allow both humans and monkeys to see in color are great targets for experimentation, as each of the three different types are linked to single gene. Humans and monkeys can’t distinguish red from green without the protein L-opsin (the “L” stands for long, as in the wavelengths of red light). By splicing the gene for L-opsin into a viral vector and injecting it behind the retinas of the test-monkeys, researchers from the University of Washington, Seattle began a lengthy, elegantly-designed experiment.

The test subjects Dalton and Sam were seated in front of a touchscreen filled with dots, similar to the Ishihara color tests you’ve probably taken at the optometrist’s office. In each trial, a cluster of red dots, when pressed, would trigger a reward of juice from a connected dispenser. Normally monkeys would press the screen randomly, searching for the spot, then repeatedly press the same area if they happened to blindly stumble upon a reward. After the gene therapy, however, the test subjects were able to pick out the cluster of red dots every time, an ability that hasn’t faded since their original treatment two years ago. They were cured. 

But “cure” isn’t exactly the right word, as Ed Yong of Not Exactly Rocket Science points out, and by making it the focal point of the headline, reporters inadvertently obscured two of the cooler parts of the story.

The first part is that all male squirrel monkeys, like Dalton and Sam, are congenitally colorblind, so a more appropriate term might be “enhance” or “upgrade.” A similar phenomenon can be seen in humans, as well; colorblindness is more prevalent in men as the gene for L-opsin is on the X-chromosome, giving women twice the chance of men of having a working copy.

This sexual dimorphism is relevant to the second, even-cooler aspect of the story: that the monkeys could make sense of the color red at all.  Once their retinas began producing l-cones, Dalton and Sam were able to perceive red almost immediately, demonstrating that their neural pathways were already capable of making sense of a kind of visual stimuli they had never before encountered. Besides the shades of the Mary’s Room thought-experiment, this suggests an impressive amount of neural plasticity present in these adult monkey brains, and a reason to be hopeful about similar ongoing efforts with humans.   

Have I also mentioned that these monkeys are totally adorable?

In any case, this is also a good time to take another look at the history of gene therapy. Researchers have been surprisingly successful in applying the technique to vision problems; color vision has been similarly induced in mice, and light sensitivity has even been restored in humans with Leber’s Congenital Amaurosis.

But yesterday was also the tenth anniversary of Jesse Gelsinger’s death. Gelsinger was a subject of one of the first human gene therapy tests, and the first to die during one. The 18-year-old had a genetic disorder that made him unable to produce an enzyme capable of breaking down ammonia. He suffered a fatal immune system response to the virus that would ostensibly rewire his liver to get rid of that chemical.

The resulting investigation of the University of Pennsylvania researchers who conducted the trial was a huge setback for gene therapy, but it did make painfully clear the importance of strong informed-consent procedures. Unfortunately, these issues were raised again under similar circumstances two years ago, when Jolee Mohr died while participating an experimental gene therapy trial for arthritis. 

Though Mohr’s death was not found to be directly caused by the viral vector, it did bring this controversy back into the spotlight. And that’s a good thing. The success with these squirrel monkeys highlights how tantalizing gene therapy is, but its potential power also demands precaution.

Full of Darwin

The new Darwin biopic Creation is so controversial its controversy has a controversy.

The film stars real-life couple Paul Bettany and Jennifer Connelly as Charles and Emma Darwin, and focused more on their relationship during the authorship of On the Origin of Species than on the development of the book and the theory behind it. It will be released in the UK next week, but has made headlines owing to its troubles finding an American distributor, which was blamed on the continued debate over the validity of evolution in parts of the US.

Bettany is a master of portraying historical academic-types, playing a Darwinian naturalist in Master and Commander and Chaucer in A Knight’s Tale. Connelly won an Oscar playing the much put-upon wife of a historical academic-type: John Nash in A Beautiful Mind.  And judging from the trailer, Creation looks to be a pretty, but pretty-run-of-the-mill, historical drama. Though a disturbingly large percentage of Americans don’t believe in evolution, plenty of any year’s film releases would be more aggressively offensive to that subset of the population. So what’s really the hold up?

There might not be any, after all. A bidding war is now reportedly underway for distribution rights. And people who have seen it, including Olivia Judson and Roger Ebert, point out that Darwin’s theory of evolution is mostly discussed as a point of contention with his wife’s devout Christianity, and the couple’s ability to resolve that tension is the focus of the film. Even with the expertly-included line about Darwin “killing God,” it sounds like the producers might have wanted to inject a little controversy into what seems like a fairly straightforward Victorian romance.

But why bother? There are plenty of lectures on the merits of evolutionary theory from which audiences can choose. If anything, the portrayal of Darwin as a father and husband will provide more of an education on how science is done. Perhaps anti-evolution folks will be swayed by this depiction of the theory as a product of human beings with all their concomitant baggage, religious and otherwise. As PZ says: “Darwin was an accomodationist.”

Each week, Seed’s Evan Lerner offers his take on the events and issues that shape science, science policy, and science journalism. Read previous Weeks in Review here, or follow him on Twitter.

Originally published September 18, 2009

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